After four years of HAART, only 39% of the Swiss HIV cohort had a CD4 cell count above 500 cells/mm3 and 16% had such low CD4 cell counts that they were at risk of opportunistic infections. Writing in the October 13th edition of the Archives of Internal Medicine investigators report that taking breaks from HAART, a viral load above 400 copies/mL at least 25% of the time or more, and older age were the key risk factors negatively affecting recovery of CD4 cell count.
CD4 cell counts were monitored at regular intervals in the 2235 members of the Swiss HIV cohort who started HAART in 1996/97. Investigators collected 48 months of data in this study, the primary purposes of which were to determine the proportion of patients who achieved a CD4 cell count of 500 cells/mm3 or more, and less than 200 cells/mm3, and the factors affecting CD4 cell recovery in the 985 patients who took continuous HAART and the 1250 individuals who took breaks from anti-HIV therapy.
At baseline the cohort showed a significant degree of immune damage as median CD4 cell count was 190 cells/mm3, a third of patients had an AIDS diagnosis and mean duration of HIV infection was over seven years. The overwhelming majority of cohort members (72.8%) were male and white (86.8%). Mean age was 38 years.
After four years of anti-HIV therapy, 69.5% of cohort members had a viral load below 400 copies/mL, and the median increase in CD4 cell count was from a baseline of 190 cells/mm3 to 423 cells/mm3. The percentage of patients with a CD4 cell count above 500 cells/mm3 increased from 9.1% at baseline to 38.8% at month 48. Of all cohort members, 15.6% had a CD4 cell count persistently below 200 cells/mm3 indicating that they were still at risk of serious illness.
Investigators found however, significant differences in CD4 cell levels after 48 months between individuals who took anti-HIV drugs all the time and those patients who interrupted their HIV therapy.
Amongst patients who took continuous HAART, 84.5% had a viral load below 400 copies/mL at month 48 and the median increase in CD4 cell count was from a baseline of 203 cells/mm3 to 486 cells/mm3. Just over half (50.3%) had a CD4 cell count above 500 cells/mm3, 26.8% had a count below 350 cells/mm3 and 6.1% at 48 months had a CD4 cell count below 200 cells/mm3.
In the treatment discontinuation group by contrast, only 53.6% had a viral load below 400 copies/mL at month 48. What’s more, median CD4 cell count was significantly lower at 343 cells/mm3. Only 29.4% reached a CD4 cell count above 500 cells/mm3 and over a quarter (25.9%) failed to maintain a CD4 cell count above 200 cells/mm3.
Of the patients who took continuous HAART, 60.1% had taken previous suboptimal NRTI therapy, and although this was associated with smaller median increases in CD4 cell count (256 cells/mm3 versus 335 cells/mm3 at 48 months, than treatment-naïve individuals, in multivariate analysis pretreatment was not an independent risk factor for poor CD4 cell recovery (p=.59).
Nor were baseline and nadir CD4 cell count before the initiation of HAART correlated with CD4 cell count recovery. However, lower baseline CD8 cell counts were associated with significantly larger increases in CD4 count (p=.008).
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Investigators also established that increasing age (p=.003) was a significant predictor of poor CD4 cell count.
On the basis of these finding the Swiss investigators argue that significant numbers of HIV-positive individuals show critically low CD4 cell counts, despite HAART. They recommend, “HAART should not be deferred to the late stages of HIV infection, although the advantages of earlier initiation of HAART have to be individually counterbalanced against potential adverse events and the rapid emergence of drug resistance.”
Further information on this website
CD4 cell count - overview
Viral load and CD4 - booklet in the information for HIV-positive people series
Kaufmann GR et al. CD4 T-lymphocyte recovery in individuals with advanced HIV-1 infection receiving potent antiretroviral therapy for 4 years. Archives of Internal Medicine 163: 2187 – 2195, 2003.